Methods have been developed in our laboratory for the deliberate selection of functional isoallelic forms of yeast alcohol dehydrogenase. The selective technique employed depends on the discovery that petite strains (those unable to respire aerobically) must have a functioning alcohol dehydrogenase in order to survive. Allyl alcohol and crotyl alcohol, harmless in themselves to yeast but oxidized by ADH to poisonous aldehydes, are presented to petite yeasts with the result that in a high proportion of the cases an electrophoretically-distinguishable enzyme mutant with altered kinetics results; the new enzyme must be able to distinguish between ethanol and the longer-chain alcohols in order for the cell to survive. We are embarking on an investigation to determine how many alterations in the primary structure can bring about such an adaptive change. We hope that this work will cast some light on the mechanisms of adaptation of multimeric enzymes to changing environmental conditions and eventually on the mechanism of action of such enzymes. We are also continuing our investigations of Drosophila enzyme polymorphisms in order to relate biochemical adaptation to environmental conditions.